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Grenoble Institut des Neurosciences Grenoble Institut des Neurosciences

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Cytoskeleton behavior in the synaptic compartment, implication in Alzheimer’s disease

Objectifs

The objective of the project is to better understand the cross-talk between microtubules and actin filaments in the post-synaptic compartment of cultured neurons in physiological and/or pathological conditions. Different animal models in which microtubules composition is altered (TTL and SVBP mice) and Alzheimer’s disease model (APP/PS1) will be used.
 

Résumé

During synaptic plasticity, dendritic spines (post-synaptic compartment) exhibit structural changes depending on actin and microtubule cytoskeletons. Microtubules and actin form dynamic networks closely related to each other. Microtubule dynamics is regulated, in part, by post-translational modifications of tubulin, including the tyrosination/detyrosination cycle: tyrosinated tubulin is a marker of dynamic microtubules and detyrosinated tubulin of stable microtubules.
Our group produced transgenic mice lacking the enzymes of the tyrosination/detyrosination cycle: tubulin tyrosine ligase (TTL) and tubulin carboxypeptidase complex VASH-SVBP. We first demonstrated the vital role of tyrosinated tubulin by analyzing the TTL KO mouse. We also described brain abnormalities and cognitive deficiencies in both, TTL and SVBP transgenic mice. Recently, we demonstrated that tubulin tyrosination regulates synaptic function and is disrupted in Alzheimer's disease.
In this project, the student will analyze the behavior and dynamics of actin and microtubules in dendritic spines of cultured neurons from WT and transgenic mice (TTL and SVBP) in which microtubules are modified.
In a next step, depending on the results obtained, he/she will perform the same set of experiments in a pathological context of Alzheimer’s disease, where tyrosination/detyrosination cycle is perturbed.
 

Méthodes

Techniques used will include cellular biology (primary neuronal cultures, neuron transfection, virus infection, immunofluorescence and confocal microscopy) and biochemistry (brain dissection, subcellular fractionation, western-blot analysis).
 

Références

 

Domaines d'expertise requis

Primary neuronal cell culture, cell biology, neurobiology, microscopy, biochemistry
 

Contacts

L. Peris (CR Inserm)
Email : leticia.peris@univ-grenoble-alpes.fr
Phone : 0456520550

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Mise à jour le 8 juillet 2022

Contacts

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